Objectives: To analyze clinical efficacy between fiberoptic ductoscopy plus ultrasound-guided minimally invasive irrigation and lesion resection in treating plasma cell mastitis (PCM), aiming to provide clinical evidence for treating PCM. Materials and Methods: 119 patients undergoing fiberoptic ductoscopy plus ultrasound-guided minimally invasive surgery in Ningxia People's Hospital were allocated into the breast duct irrigation group, and 95 counterparts receiving lesion resection in the Affiliated Hospital of Ningxia Medical University into the control group. Clinico-pathological characteristics and therapeutic effect were compared between two groups. Results: The cure rate in the breast duct irrigation group was 98.31% (117/119), significantly higher than 90.53% in the control group (p < 0.05). In the breast duct irrigation group, overall treatment time was 20.13 days, significantly longer than 15.15 days in the control group (p < 0.05). During postoperative follow-up, no recurrence was observed, significantly lower compared with 48.8% (42/86) in the control group. The degree of satisfaction in the breast duct irrigation group was 95.79% (114/119), significantly higher compared with 74.74% (71/95) in the control group. Conclusions: Fiberoptic ductoscopy plus with ultrasound-guided minimally invasive drainage is a novel and effective treatment of PCM with high cure rate, low recurrence rate, slight pain, and effectively maintains breast integrity.